The development of animal models for human herpesviruses is important to enable studies that are impractical to perform in human subjects, to provide the scientific basis to develop and test therapies, and to develop and test vaccines to prevent y-herpesvirus infection. The best candidate for an animal model for Epstein-Barr virus, the cause of infectious mononucleosis in humans which is also associated with several forms of human cancer, is Herpesvirus papio. This virus is genetically similar to Epstein-Barr virus and has similar epidemiology in the baboon colony as Epstein-Barr virus in humans. We will begin to characterize the early pathogenic events of Herpesvints papio infection in baboons, the associated clinical symptoms and laboratory changes, and the immunological responses to acute and latent infection. Two new herpesviruses have recently been described in macaques with genetic similarity to human herpesvirus type 8 (HHV8), the cause of Kaposi sarcoma, primary effusion lymphorna, and possibly associated with multiple myeloma. These are the most promising animal models for HHV8 infection. We will characterize the epidemiology of these HHV8-similar viruses in our rhesus macaque colony, and develop an in vitro propagation system to enable development of this animal model system for further studies. Development of these models will bridge the clinical experience with these diseases to the substantial molecular biology that has been characterized using cell culture and in vitro systems. These animal models will be particularly suited to facilitate development and validation of treatments, as well as vaccine candidates and preventive strategies for y-herpesvirus infections.